Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is among the top 10 leading causes of death worldwide. The treatment course for TB is challenging; it requires antibiotic administration for at least 6 months, and bacterial drug resistance makes treatment even more difficult. Understanding the mechanisms of resistance is important for improving treatment. To investigate new mechanisms of isoniazid (INH) resistance, we obtained three INH-resistant (INH-R) M. tuberculosis clinical isolates collected by the Taiwan Centers for Disease Control (TCDC) and sequenced genes known to harbor INH resistance-conferring mutations. Then, the relationship between the mutations and INH resistance of these three INH-R isolates was investigated. Sequencing of the INH-R isolates identified three novel katG mutations resulting in R146P, W341R, and L398P KatG proteins, respectively. To investigate the correlation between the observed INH-R phenotypes of the clinical isolates and these katG mutations, wild-type katG from H37Rv was expressed on a plasmid (pMN437-katG) in the isolates, and their susceptibilities to INH were determined. The plasmid expressing H37Rv katG restored INH susceptibility in the two INH-R isolates encoding the W341R KatG and L398P KatG proteins. In contrast, no phenotypic change was observed in the KatG R146P isolate harboring pMN437-katG. H37Rv isogenic mutant with W341R KatG or L398P KatG was further generated. Both showed resistant to INH. In conclusion, W341R KatG and L398P KatG conferred resistance to INH in M. tuberculosis, whereas R146P KatG did not affect the INH susceptibility of M. tuberculosis.
Tuberculosis (TB) is an infectious respiratory disease caused by Mycobacterium tuberculosis and one of the top 10 causes of death worldwide. Treating TB is challenging; successful treatment requires a long course of multiple antibiotics. Rifampicin (RIF) is a first-line drug for treating TB, and the development of RIF-resistant M. tuberculosis makes treatment even more difficult. To determine the mechanism of RIF resistance in these strains, we searched for novel mutations by sequencing. Four isolates, CDC-1, CDC-2, CDC-3, and CDC-4, had high-level RIF resistance and unique mutations encoding RpoB G 158 R, RpoB V 168 A, RpoB S 188 P, and RpoB Q 432 insQ, respectively. To evaluate their correlation with RIF resistance, plasmids carrying rpoB genes encoding these mutant proteins were transfected into the H 37 Rv reference strain. The plasmid complementation of RpoB indicated that G 158 R, V 168 A, and S 188 P did not affect the MIC of RIF. However, the MIC of RIF was increased in H 37 Rv carrying RpoB Q 432 insQ. To confirm the correlation between RIF resistance and Q 432 insQ, we cloned an rpoB fragment carrying the insertion (encoding RpoB Q 432 insQ) into H 37 Rv by homologous recombination using a suicide vector. All replacement mutants expressing RpoB Q 432 insQ were resistant to RIF (MIC > 1 mg/L). These results indicate that RpoB Q 432 insQ causes RIF resistance in M. tuberculosis.
This paper startsfrom rethinking the daily life of kids to the urbanismauthority. In recent ten years, the school-walkway projects in Taipei have re-valued the exchanging price of the old apartments built in the 1960s. The turn-key is the spatial quality of the lane along the campus. People wonder how parking, dining, and walkway for kids in the lane shape the middle-class community in Taipei. There is a critical issue of making urban 'habitable' by capitalizing the rule of time and space. The matter of the living spacereflects the critique of everyday life, especially the playtime to childhood. In the main part of the argument: how the walkway project starts the political intervention of neighborhood life. It is releasing the edge of the school to the urban function, remodelling the one way street to the community, and re-building the order of the lane space. I would like to re-test the planning of the school walkway to redevelop modern community by the corporation within Construction and Planning Agency and Ministry of the Interior, Ministry of Education, elementary schools and the neighbor communities in Taipei since 2003. In the other vision, the capitalism of kids' ground designs the geographicidentity and social difference to the habitability of urbanism.By the side of the argument, I would like toresponse how thespatial relationship of production betweenthe childhood and the neighborhoods. Representing the middle-class family living in Taipei through the transformation in-between two moviesdirected by Edward Yang:'A Brighter Summer Day '(1991)and 'AOne and A Two ' (2000). In the movies, the broken urban experience grounds the social group of kidsin the lane and to representthe class-struggle under the urbanism.
Unexpected drill breakage can be foreseen and prevented. We observed a factory and identified the warning signs of tool breakage for micro gundrills, as well as a laboratory experiment for micro drills. The vibrations of stable drilling and the vibrations that warn of tool breakage were analyzed based on the time and frequency domain features. We developed a prognostic model. We conducted physical drilling experiments on a Swiss turning machine and a laboratory research platform. Stainless steel was drilled with two types of 0.9-mm-diameter tools: 125-mm-long micro gundrills on Swiss turning machine and 25-mm-long micro drills. In both types of testing, two accelerometers were installed on the tool holder to collect two-directional vibration signals; a linear discriminant function processed the Z-axis and Y-axis signals for the telltale warning signs of impending tool breakage, and obtained a 100% classification rate. To confirm the effect of drilling disturbances on the prognostic system, the entries and exits of tools to and from workpieces were studied. The results demonstrate that both types of signal features can be used without causing any misclassification.
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